Biomineralization is a complex process orchestrated by cells, growth factors and a number of key extracellular matrix molecules, and the elucidation of factors that control the formation and maintenance of the functional mineralized matrix is critical in understanding the cause of mineralized tissue disorders. Recent studies have indicated that biglycan (BGN), a member of small leucine rich matrix proteoglycans, plays a role in bone formation/matrix mineralization by modulating osteoblast differentiation. However, the mechanisms are not well understood. This exploratory research is intended to seek a novel modulatory role of BGN in osteoblast differentiation and subsequent matrix mineralization. The hypothesis to be tested is that BGN promotes osteoblast differentiation/matrix mineralization by through its specific interaction with bone morphogenetic protein (BMP)-2. To test this hypothesis the following specific aims will be pursued: (1) to determine the binding specificity of BGN to BMP-2; (2) to investigate the effects of BGN on BMP-2-mediated osteoblastic cell differentiation; and (3) to determine the effects of BGN and BMP-2 on osteoblastic cell differentiation and matrix mineralization using osteoblastic MC3T3-E1 cell-derived clones expressing lower levels of BGN. The data obtained from this study may provide insights into a novel pathway of matrix-modulated osteoblast differentiation and mineralized tissue formation.